The purpose of the Transgenic Mouse Core is to provide two key scientific support services to members of the Program Project. The core will, in close collaboration with the principal investigator of a specific PO1 project, provide the expertise and equipment to produce transgenic mice. For some projects, the Core will use a special genetic background to make transgenics. Secondly, the core will provide services to generate null-mutant mice, again in close collaboration with the project investigator. Unlike other commonly available core support services, we have decided to organize this service on a "pay-as-you-go" basis i.e. funds are requested only to maintain the coreouse models which the individual Project Project projects propose to make will be largely generated by personnel of and will be paid by that specific project. Instruction in and advice on some of the different technologies necessary to generate mouse models will be provided for by core personnel. In addition, the Res. Spec. II paid for by the Core will perform the critical steps in these procedures (e.g., growing ES cells, microinjection). A prime consideration for this organizational structure is on the one hand, the substantial "hands-on" time involvement required for an individual project, e.g. up to 1.5 years for a null-mutant mouse, often reuiring more time and effort than usual for a normal working day. On the other hand, it is very likely that critical steps will only be performed efficiently by someone fully dedicated to and experienced in such techniques. Mouse models will have to be generated inproject 1 (Dr. Minoo), project 2 (Dr. Warburton) and project 4 (Dr. Groffen). Based onseveral of our more recent project investigatory meetings, it is likely that project 3 (Dr. DeRynch) will have a need to develop mouse model(s) (null-mutant and transgenic). The Core leader (Dr. Heisterkamp) who has many years of experience in the generation of both types of mouse models, will critically evaluate the design of each construct and will be involved in the teaching of personnel.